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p38 MAPK_(#alpha#/#beta#)和ERK_(1/2)在心肌缺氧预处理信号传递中的不同作用

黄轶峰, 龚开政, 张振刚

扬州大学第二临床学院心血管内科.江苏,扬州 225001

摘要

建立培养乳鼠心肌细胞的缺氧/复氧(A/R)损伤模型和缺氧预处理(APC)模型。在APC组,干预处理的缺氧时相给予PD98059,可以完全消除APC的延迟保护作用;在A/R组的缺氧时相加入PD98059对细胞损伤无影响;在APC组的预处理缺氧时相给予p38_(#alpha#/#beta#)抑制剂SB203580并不能消除APC的保护作用,而在A/R组的持续缺氧时相给予SB203580则可显著减轻缺氧对细胞的损伤;ERK_(1/2)和p38总活性测定表明,缺氧可激活ERK_(1/2)和p38,它们的活性在缺氧后4h时达到高峰,而经过APC处理后,两者活性高峰提前于缺氧后3h时出现,且峰值显著降低。上述结果提示,预处理过程中ERK_(1/2)的激活可能是缺氧预处理延迟保护机制中细胞信号传递的重要环节,预处理阶段p38_(#alpha#/#beta#)的活化不参与APC诱导的延迟保护信号传递过程,p38的过度激活可能是缺氧/复氧损伤过程中的一个致损伤参与因素,而预处理抑制随后持续缺氧阶段p38的过度激活可能是其保护机制的一个环节。

关键词： 生理学; 心肌保护; 缺氧; 心肌缺血预处理; 丝裂素活化蛋白激酶p38; 细胞外信号调节蛋白激酶; 大鼠

Different of ERK_(1/2) and p38 MAPK_(#alpha#/#beta#) in cellular signaling during cardiomyocyte anoxia preconditioning

Huang Yifeng, Gong Kaizheng, Zhang Zhengang

Department of Cardiology,The 2nd Clinical Medical College of Yangzhou University.Yangzhou 225001,Jiangsu

Abstract

The results obtained are as follows: (1) PD98059 (but not SB203580), administered in preconditioning anoxia phase in APC group, abolished completely the delayed protection of APC; (2) SB203580 administered in sustained anoxia phase in A/R group could relieve cell injury induced by anoxia, but not by PD98059; (3) the highest activity of ERK_(1/2) and p38 MAPK induced by anoxia appeared at 4h after the beginning of sustained anoxia. APC inhibited the over activation of both ERK_(1/2) and p38 during the following sustained anoxia. These results suggest that ERK_(1/2) activation during preconditioning may be an important link of cell signal signal transduction in the mechanism of APC delayed protection. p38_(#alpha#/#beta#) activation at the preconditioning stage dose not participate in signaling of APC delayed protection. The excessive activation of p38_(#alpha#/#beta#) is possibly a key factor in mediating cell injury induced by sustained anoxia. The inhibition of p38_(#alpha#/#beta#) excessive activation during subsequent sustained anoxia might play a role in delayed protection mechanism of APC.

Key words: Physiology;Cytoprotection anoxia;Ischemic;Preconditioning myocardial;Extracellular signal-regulated kinase p38;Mitogen-activated protein;Kinases

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引用本文：

黄轶峰, 龚开政, 张振刚. p38 MAPK_(#alpha#/#beta#)和ERK_(1/2)在心肌缺氧预处理信号传递中的不同作用[J]. 生理学报 2003; 55 (4): .

Huang Yifeng, Gong Kaizheng, Zhang Zhengang. Different of ERK_(1/2) and p38 MAPK_(#alpha#/#beta#) in cellular signaling during cardiomyocyte anoxia preconditioning. Acta Physiol Sin 2003; 55 (4): (in Chinese with English abstract).